DESCRIPTION: (Applicant's Abstract) Behavioral sensitization is a robust measure of neural plasticity that is firmly established in animal models, and as such, may underlie a number of the behavioral effects of stimulants in humans. Sensitization of these effects may contribute to the clinical symptomatology that occurs in stimulant abusers, such as the development of stimulant-induced psychosis. Behavioral sensitization may also be associated with aspects of stimulant addiction. For example, sensitization may contribute to an initial escalation in drug 'liking' that reinforces drug use. Moreover, the sensitization of psychomotor activation may share homologous neurobiological mechanisms with those underlying positive reinforcement. Sensitization may also underlie the development of pathological incentive salience (i.e.,drug craving), that leads to compulsive drug seeking and using. Human studies of sensitization to stimulants would help to clarify these issues. Unfortunately, behavioral sensitization has been rarely studied in humans. Understanding the process of sensitization in human, rather than animal models, is necessary to permit the direct examination of uniquely human drug responses that may be associated with stimulant addiction (e.g., drug "liking"). The objective of this proposal is to study the development of behavioral sensitization following repeated low-dose stimulant administration in normal human volunteers using a parallel-group, double-blind protocol. This proposal is novel in its objective to directly study behavioral sensitization in human volunteers using a parallel-group, double-blind design. The methodology proposed for this study will provide a paradigm for studying aspects of stimulant effects in humans that may be relevant for understanding and developing treatment for stimulant-induced psychosis and addiction.